A. Inducing Perspiration
Early investigators of the components of perspiration used various means to increase the quantity of perspiration which they could collect from subjects and thereafter analyze. One such means of inducing perspiration involved placing rubber gloves over the hands of a subject. When perspiration accumulated on the subject's hands, it was collected for analysis (U.S. Pat. No. 3,552,929 to Fields, et al.).
Chemical means have also been developed to accelerate the collection perspiration. For example, perspiration-inducing chemicals such as pilocarpine have been administered to increase perspiration. One way of administering these chemicals is to iontophorese them into the skin (Gibson, Pediatrics, 23:545, 1959). Permeation-enhancing chemicals, used in conjunction with abrasion to the skin, have also been employed (see, e.g., U.S. Pat. No. 4,756,314 to Eckenhoff, et al.)
Heat has been used as well in connection with the detection of analytes under the skin and with the transport of substances into a subject's body through the skin. In U.S. Pat. No. 4,401,122, Clark describes a method of arterializing the skin of a subject with heat or other means. Clark specifies that a subject's skin can be heated to 38.degree.-44.degree. C. in order to control a chemical reaction beneath the skin or in order to accelerate diffusion through the skin. Jacques, et al. (in U.S. Pat. No. 4,775,361) also describe the use of pulsed laser energy to enhance percutaneous transport.
B. Perspiration and Other Diagnostic Media
As the result of the collection and analysis of perspiration, it has been found that perspiration contains a variety of analytes of interest. In order to detect such analytes, a sufficient quantity of perspiration must first be collected from a subject so that the perspiration can be subjected to analysis. Prior art dermal patches were normally maintained on the skin of a subject for 24 hours in order to collect sufficient perspiration (see, e.g., U.S. Pat. No. 4,706,676 to Peck and U.S. Pat. Nos. 4,732,153 and 4,329,999 to Phillips). The result of using this method of collecting an analyte is a longterm integration of the concentration of the analyte in the subject's perspiration over the wear period. Specific information as to when the analyte was in the body or whether the patch was exposed to one large or multiple smaller amounts of the analyte is lost in such long-term wear.
Other diagnostic media can reveal different information regarding the concentration of an analyte. For example, the analysis of a venous blood sample reveals the concentration of an analyte in the venous circulatory system at the instant that the sample is taken. A urine sample, on the other hand, contains information as to an analyte's concentration that is somewhere in between the instantaneous information of a blood sample and the time-averaged information available from derreal patches. A urine specimen is representative of the concentration of an analyte in the body between complete voids, so that the higher the frequency of voids is, the closer the urine specimen will represent the instantaneous situation.
C. Diagnostic Kits for Collecting Perspiration
A variety of diagnostic kits for monitoring an analyte in perspiration have been developed. For example, U.S. Pat. No. 3,552,929 to Fields, et al. discloses a BAND-AID type test patch suited for determining the chloride ion concentration in perspiration as a method of diagnosing cystic fibrosis. The apparatus disclosed in Fields comprises an absorptive perspiration collecting pad with an impermeable overlying layer for the purpose of preventing evaporation. When the absorptive pad is saturated, the patch is removed from the skin and exposed to a series of strips impregnated with incremental quantities of silver chromate or silver nitrate, the color of which undergoes a well known change upon conversion to the chloride salt.
U.S. Pat. No. 4,706,676 to Peck discloses a dermal collection device which comprises a binder to prevent reverse migration of an analyte, a liquid transfer medium which permits transfer of an analyte from the derreal surface to the binder, and an occlusive cover across the top of the liquid transfer medium and binder. Peck also discloses the application of such a dermal collection device to detect various environmental chemicals to which humans are exposed. After the derreal collection device has been worn on a patient's skin for a period of time, the device is removed for analysis, which involves the chemical separation of the bound substance of interest from the binding reservoir and thereafter undertaking qualitative and/or quantitative measurement of the substance of interest by conventional laboratory techniques.
Another derreal collection device, disclosed in U.S. Pat. No. 4,756,314 to Eckenhoff, claims to quantitatively collect perspiration on a dermal patch. This patch uses a diffusion rate-limited membrane as a means to maintain a constant flow of fluid into the patch. The patch comprises an impermeable outer boundary structure, and is therefore an occlusive patch.
However, prior art derreal patches and other means of collecting perspiration are generally only useful for determining the presence of analytes which are present in perspiration in relatively high concentrations, such as halide ions. In addition, the occlusive outer layer-type devices of the prior art are susceptible to the problem of back diffusion of perspiration and/or the analytes contained therein. Occlusive devices also suffer from other problems, including changes in the skin's transport characteristics (see, Brebner, D. F., J. Physiol., 175:295-302 (1964) and Feldmann, R. J., Arch. Dermat., 91:661-666 (1965)), and the maintenance of an aqueous state below the patch, which fosters bacterial growth. Prior art dermal patches suffer from a number of other disadvantages as well, including being uncomfortable to wear and being subject to losing analytes due to fluid loss.